This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our COBRE-initiated Human Monoclonal Antibody Core Facility at OMRF is one of the few laboratories in the world that produces fully-human, full-length, antigen-specific antibodies and the only one that provides this service to COBRE investigators. Our process for making influenza-specific antibodies has been recently published (Wrammert et al., Nature. 2008 May 29; 453(7195):667-71, and Smith et al., Nature Protocols 2009; 4(3):372-84) and represents a significant breakthrough in antibody technology. With COBRE support, we have recently expanded our antigens of interest and have produced high affinity, protective antibodies to anthrax lethal toxin and various S. pneumoniae coat polysaccharides. Our primary goal is to collaborate with other COBRE investigators to define human immune responses after vaccination and to generate human monoclonal antibodies to supplement their research. We will begin at OMRF and as time and resources allow, we will expand these services to investigators at the Oklahoma University Health Sciences Center (OUHSC), Oklahoma State University and other COBRE institutions outside Oklahoma. One such collaboration with the Ballard lab at OUHSC will allow us to evaluate the generation of antibody secreting cells after acute or reactivated infection, rather than vaccination. The ability to generate antibodies after natural infection will greatly increase the number of pathogen responses we can study. These antibodies will also give us a true snapshot of the contribution of antibodies to various protective epitopes in human disease. In all these cases, the antibodies produced will be explored as passive immunotherapeutics. Finally, we will investigate microarray and Biacore technologies for the rapid initial characterization of the antibodies produced. The ability to screen antibodies simultaneously for large numbers of antigens will also allow us to study the specificities of antibodies produced by individuals with autoimmune disorders. Overall, this Core will provide services which will allow COBRE investigators to produce new therapeutics and explore new scientific directions in a variety of human immune responses in health and disease.